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Garciesculenxanthone B induces PINK1-Parkin-mediated mitophagy and prevents ischemia-reperfusion brain injury in mice
Wu,Man1,2; Lu,Guang3; Lao,Yuan zhi2; Zhang,Hong2; Zheng,Dan2; Zheng,Zhao qing2; Yi,Juan4; Xiang,Qian2; Wang,Li ming3; Tan,Hong sheng2; Zhou,Hua1; Shen,Han ming3,5; Xu,Hong xi1
2021-02-01
Source PublicationActa Pharmacologica Sinica
ISSN1671-4083
Volume42Issue:2Pages:199-208
AbstractMitophagy is a selective form of autophagy involving the removal of damaged mitochondria via the autophagy-lysosome pathway. PINK1-Parkin-mediated mitophagy is one of the most important mechanisms in cardiovascular disease, cerebral ischemia-reperfusion (I/R) injury, and neurodegenerative diseases. In this study we conducted an image-based screening in YFP-Parkin HeLa cells to discover new mitophagy regulators from natural xanthone compounds. We found that garciesculenxanthone B (GeB), a new xanthone compound from Garcinia esculenta, induced the formation of YFP-Parkin puncta, a well known mitophagy marker. Furthermore, treatment with GeB dose-dependently promoted the degradation of mitochondrial proteins Tom20, Tim23, and MFN1 in YFP-Parkin HeLa cells and SH-SY5Y cells. We revealed that GeB stabilized PINK1 and triggered Parkin translocation to the impaired mitochondria to induce mitophagy, and these effects were abolished by knockdown of PINK1. Finally, in vivo experiments demonstrated that GeB partially rescued ischemia-reperfusion-induced brain injury in mice. Taken together, our findings demonstrate that the natural compound GeB can promote the PINK1-Parkin-mediated mitophagy pathway, which may be implicated in protection against I/R brain injury.
Keywordgarciesculenxanthone B ischemia-reperfusion injury mitophagy Parkin PINK1
DOI10.1038/s41401-020-0480-9
URLView the original
Language英语
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Cited Times [WOS]:1   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.Shuguang Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai,201203,China
2.School of Pharmacy,Shanghai University of Traditional Chinese Medicine,Shanghai,201203,China
3.Department of Physiology,Yong Loo Lin School of Medicine,National University of Singapore,Singapore,Singapore
4.School of Basic Medical Science,Lanzhou University,Lanzhou,730000,China
5.Faculty of Health Sciences,University of Macau,Macao
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GB/T 7714
Wu,Man,Lu,Guang,Lao,Yuan zhi,et al. Garciesculenxanthone B induces PINK1-Parkin-mediated mitophagy and prevents ischemia-reperfusion brain injury in mice[J]. Acta Pharmacologica Sinica,2021,42(2):199-208.
APA Wu,Man,Lu,Guang,Lao,Yuan zhi,Zhang,Hong,Zheng,Dan,Zheng,Zhao qing,Yi,Juan,Xiang,Qian,Wang,Li ming,Tan,Hong sheng,Zhou,Hua,Shen,Han ming,&Xu,Hong xi.(2021).Garciesculenxanthone B induces PINK1-Parkin-mediated mitophagy and prevents ischemia-reperfusion brain injury in mice.Acta Pharmacologica Sinica,42(2),199-208.
MLA Wu,Man,et al."Garciesculenxanthone B induces PINK1-Parkin-mediated mitophagy and prevents ischemia-reperfusion brain injury in mice".Acta Pharmacologica Sinica 42.2(2021):199-208.
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